T cell responses to SARS-CoV-2 spike cross-recognize Omicron

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The SARS-CoV-2 Omicron variant possesses numerous spike protein mutations, leading to immune escape from neutralizing antibodies and reduced vaccine efficacy against infection.
• The capacity of T cell responses to target Omicron and confer protection against severe disease remains largely uncharacterized.

Purpose of the Study:

• To assess the reactivity of T cells to the Omicron variant spike protein in vaccinated and unvaccinated individuals.
• To compare T cell responses to Omicron with those against previous SARS-CoV-2 variants (Beta, Delta) and different viral proteins.

Main Methods:

• Analysis of CD4+ and CD8+ T cell responses to Omicron spike protein in participants vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent individuals (n=70).
• Comparison of Omicron cross-reactive T cell magnitude with Beta and Delta variants.
• Assessment of T cell responses to ancestral spike, nucleocapsid, and membrane proteins in patients hospitalized with Omicron infections (n=19) versus previous variants (n=49).

Main Results:

• A substantial proportion (70-80%) of CD4+ and CD8+ T cell responses targeting the spike protein were maintained against Omicron across all study groups.
• The magnitude of Omicron cross-reactive T cells was comparable to that observed for Beta and Delta variants.
• T cell responses to ancestral spike, nucleocapsid, and membrane proteins in Omicron-infected hospitalized patients were similar to those in patients hospitalized during previous waves.

Conclusions:

• Despite extensive mutations, T cell immunity induced by vaccination or prior infection largely cross-recognizes the Omicron variant.
• The preserved T cell response to Omicron warrants further investigation into its contribution to protection against severe COVID-19.